Effect of food on the bioavailability of triclabendazole in patients with fascioliasis

Lecaillon, J. B.; Godbillon, J.; Campestrini, Joelle; Náquira, César; Miranda, Luciano Cruz; Pacheco, Rosa; Mull, Robert; Poltera, A. A.

doi:10.1046/j.1365-2125.1998.00725.x

Cited by 59 publications

(34 citation statements)

References 9 publications

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“…Firstly, biliary colics occured between Days 3-7 post-therapy, whereas the maximum serum concentration of TCZ is achieved 4-10 hr post-ingestion, with elimination from the body occurring 48 hr post-ingestion. 19 Secondly, hepatic enzymes increased significantly only from Day 7 forward but not on Day 3. This means that liver enzymes usually did not increase before but only after biliary colics had begun.…”

Section: Discussionmentioning

confidence: 94%

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The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

Millán

Mull²,

Freise³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. Current chemotherapy for the treatment of infections caused by the liver fluke Fasciola hepatica is not satisfactory. Therefore, the efficacy and tolerability of triclabendazole (TCZ) was assessed for this indication. Eightytwo patients (51 female, 31 male, age 15-81 yr, mean 42 yr) with chronic or latent F. hepatica infection refractory to previous anti-helminthic chemotherapy were enrolled in a 60-day open, non-comparative trial. Patients received 20 mg/kg TCZ as two doses of 10 mg/kg administered after food 12 hr apart. Efficacy of treatment was assessed by stool microscopy, determination of Fasciola excretory-secretory antigen (FES) in feces, and by ultrasonography (US) which were systematically performed pre-therapy and on Days 1-7, 15, 30, and 60 post-therapy. For continuous safety assessment, patients were hospitalized during the first week after therapy and then monitored at home for the appearance of any adverse events. Clinical chemistry and hematology tests were carried out on Days 1, 3, 7, 15, and 60, and whenever an adverse effect occurred possibly related to therapy. Seventy-one (92.2%) of the 77 patients who completed the 60-day follow-up period became egg-negative. Efficacy of therapy was supported by the disappearance or decrease of FES antigen and of ultrasonography abnormalities. In the 6 remaining patients, parasitological cure was achieved by another single TCZ dose of 10 mg/kg on Day 60.

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Section: Discussionmentioning

confidence: 94%

“…Based on pharmacodynamic studies, the 12-hr span between the two doses appeared to be best in acheiving a maximum peak of the drug 4-12 hr later. 19 Plasma concentrations of TCZ and its metabolites were determined in order to control the absorption of TCZ.…”

Section: Methodsmentioning

confidence: 99%

The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

Millán

Mull²,

Freise³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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“…An exhaustive literature review with no language restriction produced a total of 554 (441 adults and 113 children) documented cases between 1986 and 2002 from Germany (32) (33) (61) , Switzerland (62) , France (63) (64) , Belgium (41) , Australia (29) , Venezuela (65) , Spain (66) (67) (68) , the US (69) , Japan (24) , Iran (45) (70) , Chile, (53) and Egypt (28) (44) (54) (55) , that received the veterinary formulation with no or minimal adverse events. In Peru, it has been administered since 1996 (8) (42) . In the present subgroup of participants from Asillo (n = 59) that received the veterinary TCBZ formulation, the adverse events were minimal; only 1 individual reported severe biliary colic that subsided upon treatment with antispasmodics, as documented in the safety documentation.…”

Section: Discussionmentioning

confidence: 99%

“…The meals were consumed a maximum of 30 min before drug administration to improve systemic bioavailability (41) (42) .…”

Section: Anthelmintic and Therapeutic Schemesmentioning

confidence: 99%

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children

Maco

Marcos

Delgado³

et al. 2015

Rev. Soc. Bras. Med. Trop.

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Introduction:The therapeutic scheme of triclabendazole (TCBZ), the recommended anthelmintic against Fasciola hepatica, involves 10mg/kg of body weight administered in a single dose; however, clinical trials in children are scarce. We evaluated the effi cacy and tolerability of 2 schemes of TCBZ. Methods: Eighty-four Peruvian children with F. hepatica eggs in their stools were allocated into 2 groups: 44 received 2 dosages of 7.5mg/kg each with a 12-h interval (Group I), and 40 received a single 10-mg/kg dose (Group II). Evaluation of effi cacy was based on the presence of eggs in stools, and tolerability was based on the presence of symptoms and signs post-treatment. Results: A parasitological cure was obtained in 100% of individuals from Group I and 95% of individuals from Group II. The most common adverse event was biliary colic. Conclusions: The tested scheme was effi cacious and tolerable, and it might be an optimal scheme in the region. To the best of our knowledge, this represents the largest series of children treated with TCBZ in a non-hospital setting.

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“…Triclabendazole stands out with an exceedingly high in vitro FE ratio of 10 that is not matched in the human (FE ratio 3.7). Its FE mechanism has been reported to be due to significant solubilization in fed state (26). Triclabendazole is a lipophilic (log P=6.34), low aqueous solubility drug (0.2 μg/mL in phosphate buffer), with a >20-fold higher solubility in FeSSIF compared to FaSSIF.…”

Section: In Vitro-in Vivo Relationship (Ivivr)mentioning

confidence: 99%

Food Effect in Humans: Predicting the Risk Through In Vitro Dissolution and In Vivo Pharmacokinetic Models

Mathias

Yang

Vig

et al. 2015

AAPS J

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Abstract. In vitro and in vivo experimental models are frequently used to assess a new chemical entity's (NCE) biopharmaceutical performance risk for food effect (FE) in humans. Their ability to predict human FE hinges on replicating key features of clinical FE studies and building an in vitro-in vivo relationship (IVIVR). In this study, 22 compounds that span a wide range of physicochemical properties, Biopharmaceutics Classification System (BCS) classes, and food sensitivity were evaluated for biorelevant dissolution in fasted-and fed-state intestinal media and the dog fed/fasted-state pharmacokinetic model. Using the area under the curve (AUC) as a performance measure, the ratio of the fed-to-fasted AUC (FE ratio) was used to correlate each experimental model to FE ratio in humans. A linear correlation was observed for the in vitro dissolution-human IVIVR (R 2 =0.66, % mean square error 20.7%). Similarly, the dog FE ratio correlated linearly with the FE ratio in humans (R 2 =0.74, % mean square error 16.25%) for 15 compounds. Data points near the correlation line indicate dissolution-driven mechanism for food effect, while deviations from the correlation line shed light on unique mechanisms that can come into play such as GI physiology or unusual physicochemical properties. In summary, fed/fasted dissolution studies and dog PK studies show a reasonable correlation to human FE, hence are useful tools to flag high-risk NCEs entering clinical development. Combining kinetic dissolution, dog FE model and in silico modeling one can study FE mechanism and formulation strategies to mitigate the FE risk.KEY WORDS: biorelevant dissolution; dog food effect model; food effect; in vitro-in vivo relationship.

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Effect of food on the bioavailability of triclabendazole in patients with fascioliasis

Cited by 59 publications

References 9 publications

The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children

Food Effect in Humans: Predicting the Risk Through In Vitro Dissolution and In Vivo Pharmacokinetic Models

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